A variety of vaccine formulations exist for inducing immune responses to certain pathogens, such as Herpes Simplex Virus (HSV). A focus of HSV vaccines has been the HSV type 1 and HSV type 2, glycoprotein D (gD) genes. See, G. H. Cohen et al, J. Virol., 62(8):1932-1940 (1988); H-Y. Chiang et al, J. Virol., 68(4):2529-2543 (1994); A. V. Nicola et al, J. Virol, 70(6):3815-3822 (1996); and U.S. Pat. No. 5,654,174.
Known formulations for vaccines have employed a variety of delivery vehicles for presenting such antigens as the gD gene to the mammalian immune system, so as to invoke a protective immune response against the pathogen. Such “delivery vehicles” have included as a vaccine agent heat or chemically-inactivated whole virus, protein particles of the whole virus, virus vectors, such as adenovirus and vaccinia, among others, and DNA-based vectors or plasmids. An example of the latter type of formulation for the HSV gD gene is taught in International patent application No. WO98/17820, published on Apr. 30, 1998 and U.S. Pat. No. 5,958,895. Alternatively, other delivery agents may be additives to, e.g., the plasmid based vehicles, which aid in the delivery or presentation of the antigen to the immune system. See, e.g., International patent application No. WO98/48780, published Nov. 5, 1998.
Still other variations on vaccines for a wide number of pathogens include compositions and formulations containing other agents for delivery with the antigen against which an immune response is desired. These other agents may be of the type which increase or enhance the immune response to the antigen by their own bioactivity. For example, certain cytokines and interleukins have been found to be desirable “adjuvants” for vaccine compositions. Among the more interesting of these is Interleukin-12. See, e.g., U.S. Pat. Nos. 5,723,127 and 5,571,515.
As yet another means to obtain a suitably protective immune response to any number of vaccines against pathogens, various protocols for vaccination have been proposed. For example, prior studies have demonstrated that plasmid-based vaccines can be employed to prime the immune system to a second immunization with a another form of the same antigen, such as a protein or a recombinant virus [S. W. Barnett et al, Vaccine, 15 (80):869-873 (1997); N. L. Letvin et al, Proc. Natl. Acad. Sci. USA 94:9378-9383 (1997); R. A Gramzinski et al, Molecular Med., 4:109-118 (1998); J. Schneider et al, Nature Med., 4:397 (1998); and M. Sedeguh et al., Proc. Natl. Acad. Sci. USA, 95:7648 (1998)].
Despite the wealth of information on vaccines and vaccine formulations, there continues to be a need for efficacious vaccines to induce or confer adequate protective immunity in humans to HSV, in particular.